The major objective of this research proposal is to define the roles of glucose, insulin and gastric inhibitory polypeptide in the regulation of adipose tissue lipoprotein lipase activity through a combined in vivo and in vitro approach. This enzyme is important in the removal of circulating triglyceride from plasma and has been shown to be deficient in diabetes mellitus. The resultant hypertriglyceridemia may contribute to the enhanced risk of atherosclerotic cardiovascular disease seen in diabetics. By using cultured preadipocytes the roles of glucose, insulin and gastric inhibitory polypeptide in regulating the enzyme's synthesis and secretion can be studied at a cellular level. In vivo studies in human subjects will be carried out to examine the relative roles of glucose and insulin in regulating adipose tissue lipoprotein lipase. These studies performed with the euglycemic clamp technique will test the hypothesis that high levels of plasma glucose and low levels of plasma insulin contribute independently to the lowered lipoprotein lipase activity seen in diabetics. Infusions of gastric inhibitory polypeptide will test the role of this intestinal hormone in lipid metabolism, a role previously suggested in in vitro studies. It is expected that the studies proposed will enhance the further understanding of how glucose and hormones influence lipid metabolism. In addition, these studies will potentially lead to clearer guidelines for diabetes management so that triglyceride levels can be maintained in the normal range and the risk of atherosclerosis hopefully lessened.